Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy.
Advanced stages of mycobacterial diseases such as leprosy and tuberculosis are characterized by a loss of T-cell function. The basis of this T-cell dysfunction is not well understood. The present report demonstrates major alterations in the expression of signal transduction molecules in T cells of leprosy patients. These alterations were most frequently observed in lepromatous leprosy (LL) patients. Of 29 LL patients, 69% had decreased T-cell receptor zeta-chain expression, 48% had decreased p56(lck) tyrosine kinase, and 63% had a loss of nuclear transcription factor NF-kappaB p65. An electrophoretic mobility shift assay with the gamma interferon core promoter region revealed a loss of the Th1 DNA-binding pattern in LL patients. In contrast, tuberculoid leprosy patients had only minor signal transduction alterations. These novel findings might improve our understanding of the T-cell dysfunction observed in leprosy and other infectious diseases and consequently might lead to better immunologic evaluation of patients.
Zea
A H
AH
Immunotherapy Program, Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans 70112, USA. azea@lsumc.edu
Ochoa
M T
MT
Ghosh
P
P
Longo
D L
DL
Alvord
W G
WG
Valderrama
L
L
Falabella
R
R
Harvey
L K
LK
Saravia
N
N
Moreno
L H
LH
Ochoa
A C
AC
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007918:Leprosy / Q000378:metabolism*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D016207:Cytokines; D008565:Membrane Proteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D004247:DNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)